Background: Papillary thyroid microcarcinoma (PTM) is a relatively common entity in the general population. PTM is often asymptomatic and is detected incidentally during the histopathological examination of thyroidectomy specimens from operations because of benign thyroid disease. Aims: The aims of the study are to determine the incidence of incidental papillary thyroid microcarcinomas (IPTMs) in our center, to examine the clinicopathologic characteristics of these tumors, and to present our experiences. Materials and Methods: This study includes 827 patients who underwent thyroidectomy operation in our center between January 2013 and June 2017 and were examined histopathologically in the Pathology Clinic. Patients' demographic characteristics, preoperative diagnoses, operative procedure, histopathological findings, and postoperative prognostic indexes are presented. Results and Conclusion: Of the 827 patients, 138 (16.6%) were diagnosed with a malignancy. Of these, 124 were papillary carcinoma, 5 were follicular carcinoma, 4 were lymphoma, 2 were medullary carcinoma, 2 were anaplastic carcinoma, and 1 was poorly differentiated carcinoma. The IPTM incidence rate was 8.01%; the multifocality and bilaterality rates were 23.3% and 13.3%, respectively. In 98.3% of IPTM cases, total thyroidectomies were performed, and in 1.7% of cases, subtotal thyroidectomy was performed followed by complementary thyroidectomy. No relapse or metastasis was detected in any of these cases. A careful histopathological examination of the thyroidectomy specimen is essential because IPTM is frequently skipped in fine needle aspiration cytology. We consider it best to perform total thyroidectomies because bilaterality and multifocality rates are high in IPTM. Long-term life expectancy in these tumors is quite good.

Thyroid carcinomas are the most common endocrine carcinoma and comprise 90% of all endocrine malignancies. The frequency of incidental thyroid carcinomas has been gradually increasing recently.[1],[2] In thyroid surgery, more frequent bilateral total excisions of the thyroid gland and detailed histopathological examinations of thyroid tissue are thought to be among the reasons for the recent increase.[3],[4] The prevalence of incidental papillary thyroid microcarcinomas (IPTMs) is reported to be 7.1%–16.3%.[5],[6]

If malignancy is not suspected clinically, tumors that are detected during the histopathological examination of specimens undergoing thyroidectomy operation are called “incidental.”[7] Papillary microcarcinoma is the most common type of incidental thyroid carcinoma.[8],[9] The tumor is called “papillary thyroid microcarcinoma” (PTM) if it is 1 cm or smaller.[10] The majority of PTMs are detected incidentally during histopathological examinations for benign thyroid disease.[4] The incidence of thyroid carcinoma in multinodular goiter (MNG) cases is reported to be 7.5%–13%.[11],[12] The diagnostic value of fine needle aspiration cytology (FNAC) decreases in the diagnosis of malignancy because of the increase in the number of nodules in MNG cases, and incidental thyroid carcinoma is a frequent finding in MNG.[11],[12] For this reason, many authors recommend total thyroidectomy for nonmalignant thyroid diseases such as MNG, chronic thyroiditis, and Graves' disease.[13]

Materials and Methods

This study includes 827 patients who underwent thyroidectomies in our center between January 2013 and June 2017 and were examined histopathologically in the Pathology Clinic. Patients' information was obtained from computer records and phone calls when required. Age, sex, preoperative clinical diagnoses, FNAC diagnoses, operative procedure, and histopathological findings of these cases were recorded.

Cases diagnosed or with suspected malignancy were not included. Furthermore, cases with a tumor size greater than 1 cm in the histopathological examination were also excluded. Histopathological findings such as IPTM cases' preoperative diagnoses, age, sex, tumor type, tumor size, bilaterality, multifocality, thyroid capsule invasion, and lymphovascular invasion were evaluated.

Postoperative prognostic indices were investigated, such as relapse, metastasis, and survival. The follow-up period is from the date of diagnosis to the date of relapse or the last follow-up. The patients were followed up for a mean period of 34 months (range 9–59 months). Free thyroxin (FT4) and serum thyroid-stimulating hormone (TSH) levels were analyzed to determine the suppressive dose of LT4 in the first and third postoperative months (suppression of TSH at <0.25 mIU/mL). Serum TSH, FT4, thyroglobulin (Tg), and anti-thyroglobulin antibody (anti-TgAb) were analyzed in the postoperative sixth month. Cervical lymph nodes were examined by ultrasonography (USG). Cervical USG was performed annually, and serum levels of TSH, FT4, TG, and TgAb were examined.

Result

For about 4.5 years, 827 thyroidectomies were performed in our center and 138 (16.6%) patients were diagnosed with a malignancy. Of these patients, 5 (3.6%) were diagnosed with follicular carcinoma, 4 (2.9%) were diagnosed with lymphoma, 2 (1.5%) were diagnosed with anaplastic carcinoma, 2 (1.5%) were diagnosed with medullary carcinoma, 1 (0.7%) was diagnosed with poorly differentiated carcinoma, and 124 (89.8%) were diagnosed with papillary carcinoma. Of the papillary carcinoma cases, 55 (44.3%) were diagnosed with classical papillary carcinoma (tumor size greater than 1 cm) and 69 (55.6%) were diagnosed with papillary microcarcinoma (tumor size 1 cm or smaller) [Table 1]. FNAC was not performed in 13 of the 69 papillary microcarcinoma cases. Nine cases were diagnosed with malignancy by FNAC and this group was not included in the study. In all, 47 papillary microcarcinoma cases were reported as benign by FNAC. In this study, the IPTM rate was 8.01% (60 cases).

The average age in cases with IPTM was 48 years (range 26–69 years). Of these, 53 (88.3%) were female and 7 (11.7%) were male. Of the 60 IPTM cases, 57 (95%) were operated with a prediagnosis of nontoxic MNG, whereas 3 (5%) were operated with a prediagnosis of toxic MNG. Total thyroidectomies were performed in 59 cases (98.3%). One case (1.7%) underwent a subtotal thyroidectomy and then a complementary thyroidectomy; a papillary microcarcinoma focus was observed in the other lobe of this case. In cases with incidental thyroid papillary microcarcinoma, the tumor size range was 1–10 mm with an average of 4.6 mm. The tumor was in the left lobe in 32 cases (53.3%), in the right lobe in 20 cases (33.3%), multifocal in 14 cases (23.3%), and bilateral in 8 cases (13.3%). Thyroid capsule invasion was detected in five cases (8.3%). Tumors were multifocal in four cases with capsule invasion.

Generally, cells with nuclear clearing were arranged around the fibrovascular core in histopathological examinations [Figure 1]. Tumor cells were positively stained with immunohistochemical markers such as cytokeratin 19 [Figure 2]. No lymphovascular invasion was detected in any of the cases. Other histopathological findings accompanying IPTM cases were MNG in 41 cases (68.3%), lymphocytic thyroiditis in 16 cases (26.6%), and follicular adenoma in 3 cases (5%) [Table 2].

All patients were given I-thyroxin (LT4) to suppress the TSH. Five patients with thyroid capsule invasion were treated with radioactive iodine (RAI) for 4–6 weeks after the operation. During follow-up, cervical USG was performed every 6 months for the first 2 years and then annually; serum levels of TSH, FT4, TG, and TgAb were also examined. No relapse or metastasis was detected in any of these cases, and all the patients are alive.

Discussion

Papillary thyroid carcinoma is the most frequent histopathologic type of malignant thyroid carcinoma.[9],[10] The small version is called papillary thyroid microcarcinoma which is 1 cm or smaller.[9]

The ratio of IPTM is reported to be 7.1%–16.3% in the literature.[5],[6] The IPTM ratio in this study was 8.01%, which is consistent with the literature. In the literature, the ratio of incidental carcinomas among all papillary thyroid carcinomas is reported to be 49%–75.5%.[14],[15],[16] In this study, the ratio of incidental carcinomas among all papillary thyroid carcinomas was 48.4%. It is reported that the ratio of IPTM cases has increased in recent years and the increase in total thyroidectomies is a contributing factor.[3]

Papillary thyroid microcarcinoma is often asymptomatic and is detected incidentally during the histopathological examination of thyroidectomy specimens from operations because of benign thyroid disease.[4],[17] In our study, only benign thyroid lesions were detected in 689 (83.3%) of all cases (827) who underwent thyroidectomy operation. Benign lesions according to IPTM cases were MNG in 41 cases, lymphocytic thyroiditis in 16 cases, and follicular adenoma in 3 cases.

In this study, 69 papillary microcarcinoma cases were detected and 9 (16%) were diagnosed with papillary microcarcinoma by preoperative FNAC. The remaining 60 cases were detected incidentally during the histopathological examination of the thyroidectomy specimen. In our study, 83.9% of papillary microcarcinoma cases were skipped in FNAC. As confirmed by this study, the diagnostic value of FNAC for papillary microcarcinoma is low. Because most patients have MNG and tumors are small, it is difficult to sample the area with FNAC.[9],[12] Similar to the study by Senel F et al., papillary microcarcinomas associated with thyroiditis are generally not detectable by FNAC.[18]

Careful histopathological examinations are essential for the diagnosis of papillary thyroid microcarcinoma. Because of the possibility of IPTM, careful macroscopic examinations should be performed with multiple sections on thyroidectomy specimens. Sometimes the tumor is macroscopically recognized as a broken white-colored area of just a few millimeters and sometimes it is only detectable with a microscopic examination.

The important properties of papillary thyroid microcarcinomas are multifocality and bilaterality. Multifocality is the presence of tumor in more than one focus in the same thyroid lobe or the presence of tumor in both lobes. In the literature, the multifocality rate in IPTM is reported to be 13%–41%.[16],[19],[20] In this study, the multifocality rate was 23.3% and the risk of cancer in the opposite lobe was 50% in patients with more than one focus in the same lobe. The determination of multifocality in papillary microcarcinoma is difficult in the preoperative period. Bilaterality is the presence of tumor in both the lobes. In the literature, the bilaterality rate is reported to be 20%–27.5%.[19],[20] In this study, the rate of bilaterality is lower than that reported in the literature and this rate is 13.3%. The reason for this variability is thought to be because of the use of different diagnostic criteria in different studies and may be because of the possibility of missing sight.

Lymph node involvement is common in papillary carcinoma cases. The regional lymph node metastasis was observed in 29%–40. 9% of cases.[21],[22] The lower incidence of nodal metastasis was seen in papillary thyroid microcarcinoma.[5] This rate was reported to be 0% in the study by Wang et al. and 10. 7% in the study by Vlassopoulou et al.[23],[24] Similar to the study by Wang et al.[23] no lymph node involvement was detected in any of our IPTM cases.

Total thyroidectomies are preferred in our center because of high bilaterality and multifocality rates in papillary thyroid microcarcinoma. In the literature, the mean tumor size in IPTM is below 5 mm.[16],[23] Consistent with this, the mean tumor size in this study was 4.6 mm.

Treating patients with differentiated thyroid carcinoma involves primary adjuvant procedures such as hemithyroidectomy, complementary thyroidectomy, RAI therapy, LT4 therapy, and suppressing TSH levels. However, a very low rate of recurrence in a large series of IPTM cases does not suggest the use of adjuvant treatment, except the suppression of TSH levels with LT4 treatment.[25]

Central neck dissection or modified neck dissection is recommended if there is cervical lymphadenopathy.[26],[27] Neck dissection was not performed because no cervical lymphadenopathy was detected in our cases. Total thyroidectomies were performed in 98.3% of cases; subtotal thyroidectomy was performed in 1.7% of cases (one case). In this case, complementary thyroidectomy was performed, and papillary microcarcinoma focus was detected in the lobe.

Adjuvant radioiodine therapy is recommended if there is tumor multifocality, lymph node metastasis, and vascular invasion.[28] RAI is unnecessary in the majority of patients because of low risk of recurrence.[25] In this study, five patients with thyroid capsule invasion were treated with RAI.

The recurrence rate in IPTM is very low and is reported to be 0%–5%.[5],[15],[16] In this study, no recurrence or metastasis was observed in any of the cases.

In conclusion, the incidence rate of IPTM is high because of benign thyroid disease. FNAC is not very reliable in diagnosing papillary thyroid microcarcinoma. Therefore, a careful histopathological examination is essential. Multifocality and bilaterality are the main pathological features of papillary thyroid microcarcinoma, and total thyroidectomies are preferred.